A prospective, double-blind, randomized, controlled clinical trial compared the efficacy and safety of fixed combinations of low-molecular weight heparin or standard unfractionated heparin plus dihydroergotamine mesylate in the prevention of deep vein thrombosis in high-risk patients undergoing elective major abdominal surgery. Two hundred patients, with a mean age of 66.6 years and almost half with malignancy, were allocated to receive either 5,000 IU unfractionated heparin plus 0.5 mg dihydroergotamine mesylate twice daily or 1,500 IU low-molecular weight heparin plus 0.5 mg dihydroergotamine mesylate once daily together with one placebo injection per day. Treatment was commenced 2 hours preoperatively and continued for at least 7 days. The incidence of deep vein thrombosis, determined by radiolabelled fibrinogen uptake and phlebography, was 11 percent in the unfractionated heparin plus dihydroergotamine mesylate group and 11.4 percent in the low-molecular weight heparin and dihydroergotamine mesylate group. Neither these figures nor those for major proximal thrombi proved significantly different. Of the four parameters used to assess hemorrhagic complications, only the decrease in postoperative hemoglobin levels in the low-molecular weight and dihydroergotamine mesylate group reached statistical significance. These results indicate that once-daily prophylaxis with a combination of low-molecular weight heparin and dihydroergotamine is safe, effective, and convenient in high-risk patients undergoing major abdominal surgery.